3nrx

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Insights into anti-parallel microtubule crosslinking by PRC1, a conserved non-motor microtubule binding proteinInsights into anti-parallel microtubule crosslinking by PRC1, a conserved non-motor microtubule binding protein

Structural highlights

3nrx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.75Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRC1_HUMAN Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle.[1] [2] [3] [4] [5] [6] [7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Formation of microtubule architectures, required for cell shape maintenance in yeast, directional cell expansion in plants and cytokinesis in eukaryotes, depends on antiparallel microtubule crosslinking by the conserved MAP65 protein family. Here, we combine structural and single molecule fluorescence methods to examine how PRC1, the human MAP65, crosslinks antiparallel microtubules. We find that PRC1's microtubule binding is mediated by a structured domain with a spectrin-fold and an unstructured Lys/Arg-rich domain. These two domains, at each end of a homodimer, are connected by a linkage that is flexible on single microtubules, but forms well-defined crossbridges between antiparallel filaments. Further, we show that PRC1 crosslinks are compliant and do not substantially resist filament sliding by motor proteins in vitro. Together, our data show how MAP65s, by combining structural flexibility and rigidity, tune microtubule associations to establish crosslinks that selectively "mark" antiparallel overlap in dynamic cytoskeletal networks.

Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein.,Subramanian R, Wilson-Kubalek EM, Arthur CP, Bick MJ, Campbell EA, Darst SA, Milligan RA, Kapoor TM Cell. 2010 Aug 6;142(3):433-43. PMID:20691902[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Jiang W, Jimenez G, Wells NJ, Hope TJ, Wahl GM, Hunter T, Fukunaga R. PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. Mol Cell. 1998 Dec;2(6):877-85. PMID:9885575
  2. Mollinari C, Kleman JP, Jiang W, Schoehn G, Hunter T, Margolis RL. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J Cell Biol. 2002 Jun 24;157(7):1175-86. Epub 2002 Jun 24. PMID:12082078 doi:10.1083/jcb.200111052
  3. Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N, Todokoro K. Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 2004 Aug 18;23(16):3237-48. Epub 2004 Aug 5. PMID:15297875 doi:10.1038/sj.emboj.7600347
  4. Zhu C, Jiang W. Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):343-8. Epub 2004 Dec 29. PMID:15625105 doi:0408438102
  5. Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, Barr FA. KIF14 and citron kinase act together to promote efficient cytokinesis. J Cell Biol. 2006 Jan 30;172(3):363-72. Epub 2006 Jan 23. PMID:16431929 doi:jcb.200511061
  6. Wolfe BA, Takaki T, Petronczki M, Glotzer M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 5;7(5):e1000110. doi: 10.1371/journal.pbio.1000110. Epub 2009, May 26. PMID:19468300 doi:10.1371/journal.pbio.1000110
  7. Subramanian R, Wilson-Kubalek EM, Arthur CP, Bick MJ, Campbell EA, Darst SA, Milligan RA, Kapoor TM. Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein. Cell. 2010 Aug 6;142(3):433-43. PMID:20691902 doi:10.1016/j.cell.2010.07.012
  8. Subramanian R, Wilson-Kubalek EM, Arthur CP, Bick MJ, Campbell EA, Darst SA, Milligan RA, Kapoor TM. Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein. Cell. 2010 Aug 6;142(3):433-43. PMID:20691902 doi:10.1016/j.cell.2010.07.012

3nrx, resolution 1.75Å

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